The metabolism of amino acids is complex and highly regulated. While cells are capable of creating most amino acids de novo, the import of amino acids into cells via specific amino acid permease proteins is vital for maintaining the appropriate and complete availability of all necessary amino acids. This is particularly important during cell proliferation and differentiation. In addition to their role as protein building blocks, amino acids also serve as precursors for a variety of other important macromolecules. For example, the hormone thyroxine, the pigment melanin, and the neurotransmitters histamine, epinephrine, and serotonin are produced from various amino acid precursors, including histidine, tyrosine, and tryptophan. A component of sphingolipid formation, sphingosine, is derived from serine. Porphyrin rings, which are components of heme molecules, use glycine as a nitrogen donor. Significant portions of the ring structures of purines and pyrimidines, components of nucleic acids, are formed from the breakdown of numerous amino acids. Amino acids are also important in energy metabolism. Unlike fatty acids and glucose, amino acids cannot be stored in the cell, so excess amino acids are fed into the citric acid cycle to produce energy molecules including fatty acids, ketone bodies, and glucose. Thus, precise control of amino acid metabolism is extremely important to both proliferating and non-proliferating cells.
The E16 gene, cloned from human peripheral blood lymphocytes, encodes a 241 amino acid integral membrane protein with multiple predicted transmembrane domains. (Gaugitsch, H. W. et al. (1992) J. Biol. Chem. 267:11267-11273.) E16 gene expression is closely linked to cellular activation and division. In myeloid and lymphoid cells, E16 transcripts are rapidly induced and rapidly degraded after stimulation. This pattern of expression resembles the kinetics seen for proto-oncogenes and lymphokines in the T cell system. Elevated levels of E16 expression were detected in colonic, gastric, and breast adenocarcinomas, and in lymphoma, while little or no E16 expression was detected in normal (non-cancerous) human tissues such as adult brain, lung, liver, colon, esophagus, stomach, or kidney, nor in four-month fetal brain, lung, liver, or kidney. (Wolf, D. A. et al. (1996) Cancer Res. 56:5012-5022; Gaugitsch et al., supra.) E16 was detected in every cell line tested. Its presence in rapidly dividing cell lines and its absence in human tissues with low proliferative potential suggest a direct involvement of E16 protein in the cell division process. This hypothesis is supported by the recent identification of a putative human amino acid permease (haap) (GI 1665759), that shares 45% identity with the E16 protein. (Nagase, T., et al. (1996) DNA Res. 3:321-329.) This sequence similarity suggests that amino acid permeases, such as haap and, possibly E16, are up-regulated in tumor cells and other rapidly-dividing cells, where they help provide important building blocks for energy metabolism, biochemical synthetic pathways, and protein synthesis.
The discovery of a new amino acid permease homolog and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, treatment, and prevention of cancer, inflammatory/autoimmune disorders, and cell proliferation disorders.